Betain
Methyl group donor from sugar beet and reserve pathway in the methionine cycle. Lowers homocysteine in a dose-dependent manner and improves maximum strength in the lower body.
Auch bekannt als: Betain, TMG, Trimethylglycin, Betaine Anhydrous
What it is
Betaine is glycine, which has three methyl groups attached to its nitrogen atom. Hence the chemical name trimethylglycine. The quadruple nitrogen has a fixed positive charge, the carboxyl group at the other end has a negative charge. The molecule is therefore a zwitterion: neutral on the outside, highly polar on the inside. It dissolves excellently in water, but does not interfere with the charge balance of the cell. It is precisely this combination that makes it one of the few substances that a cell can store in large quantities without disrupting its metabolism.
It was discovered in the 19th century in sugar beet, Beta vulgaris, hence the name. The richest food sources are wheat bran and wheat germ with over one gram per 100 g, followed by quinoa, spinach, beetroot and seafood. A mixed diet provides around 0.5-2g per day. If you eat few whole grains and few leafy vegetables, you can be significantly lower.
Betaine is not a vitamin, the body produces it itself. The starting material is choline: in the Mitochondria from Liver and kidney The choline dehydrogenase oxidizes choline to betaine aldehyde, and a second dehydrogenase further oxidizes it to betaine. This step is a two-way street. Betaine never becomes choline again; it can only leave the body via the one reaction that is discussed in the next section.
How it works
The one reaction
Betaine has precisely one enzymatic role in human metabolism. The enzyme betaine homocysteine methyltransferase, or BHMT for short, takes one of the three methyl groups and transfers it to homocysteine. What remains is methionine and dimethylglycine. BHMT is located almost exclusively in the liver and kidneys, and there in large quantities: the liver is the organ with the highest betaine content of all.
Dimethylglycine is then broken down into glycine via sarcosine. The carbon units split off end up in the folate pool and are therefore still available to the body for methylation. None of the three methyl groups in betaine are lost.
Motif: Kreislauf im Uhrzeigersinn: Methionin wird zu SAM, SAM gibt seine Methylgruppe an die Zielreaktionen ab, angedeutet durch DNA und Kreatinsynthese, übrig bleibt Homocystein. Von Homocystein führen drei Wege zurück oder hinaus: die Transsulfurierung nach außen, der Folat- und B12-Weg zurück zu Methionin, und der Betainweg über BHMT, ebenfalls zurück zu Methionin. Der Betainweg hervorgehoben, die beiden anderen zurückhaltend. Purpose: Zeigt, dass Homocystein kein Fremdstoff ist, sondern der unvermeidliche Rest jeder Methylierung, und an welcher einzelnen Stelle Betain ansetzt. Style: flat, factual vector graphic in the style of a textbook blackboard, clear contours, few flat colors, no photorealism, no textures, no drop shadows, no spatial lighting, calm monochrome background, no text in the image. Label: „Methionin“, „SAM“, „Homocystein“, „Betain“, „BHMT“. Format: across, about 16:9
Why this one reaction makes so much difference
Methylation is one of the most common chemical changes in the body. Methyl groups end up on DNA and control which genes are read. They end up on histones, on proteins, on neurotransmitters, on phospholipids. Over two hundred different methyltransferases carry out these reactions, and they all get the methyl group from the same substance: S-adenosylmethionine, or SAM for short, formed from methionine and ATP.
Once SAM has lost its methyl group, what is left is S-adenosylhomocysteine, which is immediately converted into adenosine and Homocysteine is split. Homocysteine is therefore not a foreign substance or an error in the system. It is the inevitable waste product of every single methylation. Those who methylate a lot produce a lot of homocysteine.
The body has three ways to break it down:
- Transsulfurization. The cystathionine beta synthase attaches homocysteine to serine and thus finally removes it from the circulation, via cystathionine to cysteine and on to glutathione. The enzyme needs Vitamin B6 as a cofactor.
- Remethylation via methionine synthase. It gets the methyl group from folate metabolism and needs Vitamin B12 as a cofactor. This pathway runs in virtually every cell.
- Remethylation via BHMT. The betaine pathway. It does not contain B12 or folate and is therefore the reserve when the folate pathway reaches its limit.
About half of the homocysteine in the liver is converted back via the betaine pathway. Anyone who consumes betaine increases the capacity of this pathway and the homocysteine level drops measurably.
What strength training has to do with it
Of the over two hundred methyltransferases, two are crucial in terms of quantity; together they consume the lion's share of all methyl groups. One is phosphatidylethanolamine-N-methyltransferase, which is responsible for phosphatidylcholine Cell membranes manufactures. The other is this Guanidinoacetate methyltransferase, and that represents Creatine here.
Creatine synthesis occurs in two steps across two organs. In the kidney, the arginine-glycine amidinotransferase combines arginine and glycine to form guanidinoacetate. This travels through the blood to the liver, where guanidinoacetate methyltransferase transfers a methyl group from SAM to it. The creatine is ready. So every single creatine molecule that the body produces itself costs a methyl group and leaves behind a molecule of homocysteine.
An adult's body converts around 1.5 to 2 percent of its creatine stock every day. For a muscular person, that's around two grams a day, which either comes from food or has to be rebuilt using methyl groups. This is not a side note of metabolism, but rather the largest single item. Animal experiments show it directly: If creatine is fed, the methylation load and thus homocysteine production decreases; if the precursor guanidinoacetate is fed instead, it increases.
This leads to a nice side effect that is rarely mentioned: who Creatine Supplemented saves the body exactly the methyl groups that betaine supplies. The two substances attack at opposite ends of the same balance.
Betaine as an osmolyte
In addition to its role as a methyl group donor, betaine has a second, completely independent function. Cells absorb it via their own transporter, BGT1, which transports betaine into the cell interior together with sodium and chloride. This is best studied in the kidney medulla, where the cells are exposed to extreme salt concentrations. If the external osmolarity increases, the transcription factor TonEBP migrates into the cell nucleus and allows more transporters to be built. The cell fills with betaine and maintains its volume without changing its ion balance. Betaine also stabilizes the folding of proteins, which is why it is also used as an additive in the laboratory.
Cell volume itself is a signal. When a cell swells, its metabolism shifts towards structure: protein synthesis increases, protein degradation decreases, via mTOR-dependent signaling pathways. If it shrinks, the balance tilts in the other direction. This connection has been clearly demonstrated in liver cells and is the same mechanism that explains part of the effect of creatine.
This is where the secured ends. It is not clear how much betaine the human skeletal muscle cell actually stores when supplemented and whether the resulting volume change is large enough to explain the measured increases in strength. The mechanism is plausible and proven in its individual parts, the causal chain up to the dumbbell is not.
What the studies show
Homocysteine
Here the data is clear and dose-dependent. In a controlled study with four groups of 19 people each over six weeks, fasting homocysteine levels were 12 percent lower compared to placebo with 1.5 g of betaine per day, by 15 percent with 3 g and by 20 percent with 6 g. After exposure to methionine, which specifically puts pressure on the system, the increase was 23, 30 and 40 percent lower. Even amounts in the range of normal food intake have a measurable effect.
You can also see where the limit is on the curve. The jump from 1.5 to 3 g brings three percentage points, doubling from 3 to 6 g only five. The system saturates because the capacity of the BHMT pathway is finite and the excess is simply eliminated.
It is important to classify this effect. Elevated homocysteine levels are an established risk marker for cardiovascular disease. Whether lowering this marker also prevents the disease is another question, and it has been thoroughly investigated: A Cochrane review of 15 randomized studies with 71,422 participants found no difference in homocysteine-lowering measures in heart attacks (relative risk 1.02) and no difference in overall mortality (1.01). Only in the case of stroke was there a small advantage (0.90). These studies used B vitamins, not betaine, but they make the crucial statement: Homocysteine is well established as a marker, but weak as a target. A lower value is an indication of a relieved methyl metabolism, not a promise of a longer life.
Power and performance
The current meta-analysis summarizes 17 studies with 317 participants. For the maximum strength, there is a standardized mean difference of 0.47 (95% confidence interval 0.04 to 0.89). Broken down, this effect comes almost entirely from the lower body (0.49), with nothing left in the upper body. Jump height improves slightly (0.36), betaine has no effect on sprint performance or muscle endurance.
An older review of seven individual studies came to a more skeptical conclusion, with only two of them showing any improvement at all. The contradiction is only an apparent one: an effect of this size cannot be reliably demonstrated with twelve or fifteen participants per group. This is exactly why studies are summarized.
When it comes to body composition, things are thin. The most cited work gave trained men 2.5 g per day for six weeks and saw more favorable development of muscle and fat mass. The number of participants was small, confirmation from larger studies is pending.
Dosage
- 2.5g per day for the performance effect, which is the dose of practically all positive studies
- Usually as twice 1.25 g. The time of intake does not matter; betaine works by building up tissue levels, not acutely
- No charging required. The effect is measurable from around seven days of continuous use
- For the homocysteine effect, 3-6 g per day is significantly more effective than 1.5 g
The powder tastes salty-bitter and is highly hygroscopic; it draws water out of the air and clumps together. Store dry and closed.
Side effects
Little happens in the usual quantities. How resilient the substance is is shown by its medical use: for homocystinuria, a congenital defect of cystathionine beta synthase, betaine is an approved medicine and is given permanently in amounts of 6 g or more per day, based on weight in children. The experience with this extends over decades. However, two points remain to be mentioned.
Fishy body odor. Betaine that is not absorbed reaches the large intestine. There, bacteria split off the methyl groups, producing trimethylamine, a volatile amine that smells like fish and is released through breath, sweat and urine. Normally, the liver enzyme FMO3 oxidizes it beforehand to form the odorless TMAO. The extent to which it occurs depends on two factors: the amount that reaches the colon without being absorbed, i.e. the single dose, and the patient's own FMO3 activity. Anyone who carries a weak variant of the enzyme smells earlier; the bilateral deficiency is congenital trimethylaminuria. At 2.5 g per day the smell is rare, but at 6 g it occurs. What you can do: Divide the daily amount into two to three individual doses and take it with a meal so that less goes on without being absorbed. If that's not enough, the dose is too high. There is no permanent damage; once you stop using it, the smell goes away within a few days.
TMAO. The same path leads to a substance that has been debated for years. TMAO has been linked to atherosclerosis and cardiovascular events in observational studies and animal experiments; the debate was sparked by a paper on dietary choline. It has not been investigated whether 2.5 g of betaine per day makes a measurable difference. However, it is possible to name who would be most likely to be affected: TMAO will be handled by them kidney excreted; if the kidney function is impaired, the level rises anyway. What you can do: Anyone who has a noticeable value Creatinine and eGFR leaves out the high doses and sticks with the 2.5 g, which is enough for the performance effect anyway. For everyone else, this is an open question and not a finding.
Classification
Betaine is the rare case where the biochemistry is fully understood and the performance effect is still small. The two should be thought of together: methyl metabolism is real, the homocysteine effect is dose-dependent and reproducible, and the connection to creatine synthesis explains why strength athletes of all people have a need for this. What this results in on the dumbbell is 0.47 standardized mean differences in the maximum strength of the lower body. Converted to one Maximum force output That's a few kilos, not a new person.
Who it's worth for: Anyone who has protein and Creatine has covered who trains heavily and with the big lower body exercises and who wants to get a small but proven effect for two euros a month. Who is not for: Anyone who expects a noticeable change. Betaine belongs to the category of products that you measure on the bar and not in the mirror.
Sources
- Craig SA. Betaine in human nutrition. Am J Clin Nutr. 2004. PubMed
- Brosnan JT et al. Methylation demand: a key determinant of homocysteine metabolism. Acta Biochim Pol. 2004. PubMed
- Kempson SA et al. The betaine/GABA transporter and betaine: roles in brain, kidney, and liver. Front Physiol. 2014. PubMed
- Stead LM et al. Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. Am J Physiol Endocrinol Metab. 2001. PubMed
- Edison EE et al. Creatine synthesis: production of guanidinoacetate by the rat and human kidney in vivo. Am J Physiol Renal Physiol. 2007. PubMed
- Schliess F et al. Cell hydration and mTOR-dependent signalling. Acta Physiol (Oxf). 2006. PubMed
- Olthof MR et al. Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women. J Nutr. 2003. PubMed
- Marti-Carvajal AJ et al. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev. 2017. PubMed
- Zawieja E et al. Effects of chronic betaine supplementation on exercise performance: systematic review and meta-analysis. J Sports Sci. 2024. PubMed
- Ismaeel A. Effects of betaine supplementation on muscle strength and power: a systematic review. J Strength Cond Res. 2017. PubMed
- Cholewa JM et al. Effects of betaine on body composition, performance, and homocysteine thiolactone. J Int Soc Sports Nutr. 2013. PubMed
- Morris AA et al. Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency. J Inherit Metab Dis. 2017. PubMed
- Wang Z et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011. PubMed
- Li M et al. Fish odour syndrome. CMAJ. 2011. PubMed
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